To identify alcoholism risk genes, we are collecting and testing for linkage families from Indian populations which are relatively homogeneous and in which alcoholism is highly prevalent. This study also addresses the genetic epidemiology and psychiatric comorbidity of alcoholism in Indians. Studies are underway at three sites. Two hundred Cheyenne Indians have been clinically evaluated and their cell lines immortalized. Genetic linkage is underway on this group. At Jemez Pueblo, data and cell lines have been collected for 100 subjects. A study on the Pima Indians is in progress. Frequency of the inactive ALDH and of flushing is low in Cheyenne Indians, as was previously shown by Li et al. for Southwest Pueblo Indians. A synthesis of available population and molecular genetic data indicates a probable role for a selective force (such as a disease) in maintaining the inactive ALDH variant at high frequency in Oriental and South American Indian populations.